The beta-amyloid peptide and the cerebral plaques that it forms are likely to be either the direct or indirect cause of Alzheimer's disease (AD). This peptide is produced in both the brain and peripheral tissues by cleavage from a common cell-surface precursor protein. Soluble beta-amyloid exists free in the blood and cerebrospinal fluid while "insoluble" aggregates are deposited in the brain as amyloid plaques. The soluble and insoluble forms of beta-amyloid present within Alzheimer's patients appear to be in dynamic equilibrium. We will displace this equilibrium away from the brain by generating peptide-specific antibodies in a transgenic mouse model of Alzheimer's disease. Restricted to the peripheral circulation, these antibodies will sequester beta-amyloid peptide in the blood and by doing so gradually deplete intercommunicating peptide levels in the brain. Decreased concentrations of beta-amyloid in the brain should reduce the size and number of brain plaques or delay their appearance. The study would establish a causal relationship between amyloid deposits and memory impairment in these transgenic mice. Moreover, by virtue of their ability to perturb the soluble beta-amyloid equilibrium, our expressly designed beta-amyloid antigens and antibodies would form a basis for the immunotherapy of Alzheimer's disease. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE